Immunohistochemical staining for Ki-67 antigen, carcinoembryonic antigen, and p53 in the differential diagnosis of glandular lesions of the cervix

Cytoplasmic carcinoembryonic antigen (CEA) positivity assists in the distinction of benign and malignant glandular lesions of the cervix, but some cases remain problematic. The accumulation of p53 protein and an increased proliferative index, as measured by the expression of Ki-67 antigen have not been used as adjuncts to the diagnosis of these lesions. Immunohistochemical stains for CEA, p53 protein, and Ki-67 antigen were performed on 31 formalin-fixed, paraffin-embedded endocervical lesions including invasive adenocarcinoma, adenocarcinoma in situ, adenoma malignum, tunnel clusters, florid microglandular hyperplasia, mesonephric remnants, florid glandular hyperplasia, atypical glandular hyperplasia, and normal controls. Ki-67 antigen expression was quantitated as negligible, low, moderate, or high on the basis of the percentage (<5%, 5-10%, 11-40%, >40%, respectively) of glandular nuclei that were positive with MIB-1 antibody. Strong staining of more than 10% of the glandular epithelial nuclei was interpreted as positive for p53 protein overexpression. CEA positivity was determined by either diffuse or focal cytoplasmic, staining of columnar epithelial cells equalling glycocalyceal staining in intensity. The combination of CEA positivity and a moderate-to-high proliferative index was limited to cases of invasive adenocarcinoma, adenoma malignum, and adenocarcinoma in situ, as compared with benign glandular lesions (P = 0.005). A high Ki-67 proliferative index and/or CEA positivity were features of malignant lesions rather than benign mimickers; there were no false positives or false negatives. Similarly, only malignant neoplasms shared a combination of p53 overexpression and CEA positivity (P = 0.043). The combination of cytoplasmic CEA positivity in glandular cells and a moderate-to-high Ki-67 proliferative index is diagnostic of malignancy in endocervical lesions. With the exception of florid microglandular hyperplasia, p53 expression is only seen in neoplastic lesions of the endocervix. An immunohistochemical battery consisting of MIB-1 (Ki-67), p53 protein, and CEA is useful in discriminating between benign and malignant endocervical lesions.